Mechanism of estrogen action studies in the human

The interaction of both estradiol and estrone with human endometrial tissue obtained during the proliferative phase of the menstrual cycle has been examined by in vivo and in vitro techniques. Infusions of the tritium-labeled steroids resulted in tissue: plasma concentration gradients for both steroids, although the tissue levels of estrone were generally lower than those of estradiol. Little if any conversion of estrone to estradiol within the tissue was observed. Sucrose density gradient ultracentrifugal analysis of cytoplasmic and nuclear extracts following incubations with [³H]-estradiol revealed the presence of 8S and 4-5S receptors, respectively. While cytoplasmic binding of estrone was observed, transfer to the nucleus, although possible, was not proven. The human estrogen receptor system was found to be more labile than that of other species. Finally, evidence has been obtained which suggests that intranuclear conversion of estradiol to estrone may constitute a "release" mechanism for estradiol turnover in target cells.